Recruiting
Phase 2

Botensilimab & Balstilimab

Sponsor:

City of Hope Medical Center

Code:

NCT07595874

Conditions

Advanced Colon Adenocarcinoma

Advanced Colorectal Adenocarcinoma

Advanced Rectal Adenocarcinoma

Stage IIB Colon Cancer AJCC v8

Stage IIB Rectal Cancer AJCC v8

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Balstilimab

Biospecimen Collection

Botensilimab

Computed Tomography

Magnetic Resonance Imaging

Study Details

Brief summary:

This phase II trial tests how well giving botensilimab and balstilimab prior or to surgery (neoadjuvent) works for the treatment of colorectal cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and that can be removed by surgery (resectable) colorectal cancer. Immunotherapy with monoclonal antibodies, such as botensilimab and balstilimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving botensilimab and balstilimab before surgery may make the tumor smaller. Giving neoadjuvant botensilimab and balstilimab may be effective for the treatment of advanced resectable colorectal cancer.

Conditions

Advanced Colon Adenocarcinoma

Advanced Colorectal Adenocarcinoma

Advanced Rectal Adenocarcinoma

Stage IIB Colon Cancer AJCC v8

Stage IIB Rectal Cancer AJCC v8

Study ID

NCT07595874

Start date

Dec 27, 2026

Status verified date

Jun, 2026

Completion date

May 27, 2027

Anticipated

Primary completion date

May 27, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Documented informed consent of the participant and Legally Authorized Representative (when applicable)

  • Assent, when appropriate, will be obtained and documented for adults lacking capacity per institutional guidelines
  • Agreement to allow the use of tissue from past and future surgery and standard of care biopsies
  • Age: ≥ 18 years
  • Eastern Cooperative Oncology Group (ECOG) ≤ 2
  • Histologically confirmed or cytologically confirmed colorectal adenocarcinoma. Patients with high grade dysplasia on histology plus unequivocal endoscopic or radiological evidence of invasive cancer are eligible.

Patients diagnosed with rectal cancer who will be treated like colon cancer with curative-intent surgery first and no radiation are also eligible, including:

  • Upper rectum or rectosigmoid considered as non-rectal and not undergoing neoadjuvant treatment
  • The tumor component should not extend to less 12 cm from the anal verge.
  • Any patient with rectal cancer for whom radiotherapy is not advised is included in this protocol (i.e., excluding rectal adenocarcinomas warranting treatment with chemoradiation)

  • Microsatellite stability by mismatch repair by immunohistochemistry, polymerase chain reaction and/or other Clinical Laboratory Improvement Amendments (CLIA) certified next generation sequencing. Only patients with mismatch repair proficient or microsatellite stable (pMMR/MSS) tumors are allowed to enroll in the study
  • Candidate for and planning a curative resection. Must have surgeon identified
  • T4, N+ (American Joint Committee on Cancer \[AJCC\] TNM staging criteria), or both by central radiographic assessment.
  • Note: Patients with T3N0 stage IIA are excluded. Stage IIB, IIC, IIIA, IIIB, and IIIC are included. Patients with stage IV disease are excluded

  • Absolute neutrophil count (ANC) ≥ 1,500/mm\^3
  • Platelets ≥ 75,000/mm\^3
  • NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment

  • Hemoglobin ≥ 8 g/dL
  • NOTE: Red blood cell transfusions are permitted. Patients should not have active clinically significant bleeding requiring regular transfusions. Iron infusions are also allowed

  • Total bilirubin ≤ 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease, in which case the liver function tests must meet the other eligibility in the protocol)
  • Aspartate aminotransferase (AST) ≤ 3.0 x ULN
  • Alanine aminotransferase (ALT) ≤ 3.0 x ULN
  • Creatinine clearance of ≥ 40 mL/min per the Cockcroft-Gault formula
  • Women of childbearing potential (WOCBP): negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Agreement by females and males of childbearing potential\* to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 9 months for women, and at least 6 months for men, after the last dose of oxaliplatin therapy. If patients discontinue oxaliplatin more than 9 months (females) or 6 months (males) before discontinuation of balstilimab and/or botensilimab, females and males of childbearing potential must use an effective method of birth control or abstain from sexual activity for the course of the study through at least 120 days after the last dose of balstilimab and/or botensilimab.
  • Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only).
  • The following are acceptable birth control methods for this study: Surgical sterilization (tubal ligation or hysterectomy for women, or vasectomy for men), double-barrier methods (i.e. condoms, diaphragm, cervical cap, or sponge, used together with spermicidal gel or foam), intrauterine device (IUD) (i.e. Progestin, Copper), or hormonal contraceptives (birth control patches, implants, pills, rings, or injections)

Exclusion Criteria:

  • Any treatment for colorectal cancer prior to enrollment that includes (but not limited to) chemotherapy, surgery, radiation, immunotherapy and/or biological therapy.

  • Note: Surgical intervention e.g. a diverting ostomy to relieve an obstruction from colorectal cancer, those patients will be allowed to enter the study as long as no distant metastatic disease
  • Patients with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) within 14 days or another immunosuppressive medication within 30 days of the first dose of study treatment. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease
  • Prior allogeneic organ transplantation
  • Herbal medications that require a prescription or are anti-cancer
  • Other active malignancy. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Please note: patients with more than 1 colorectal cancer tumor at diagnosis (as long as no stage IV disease) are allowed to participate. Pathologic response to each of the tumors will be examined
  • Active acute colonic obstruction. Patients whose obstruction is relieved by a successful defunctioning stoma are allowed once recovered to a fitness level consistent with the other eligibility criteria
  • Clinically significant uncontrolled illness
  • Females only: Pregnant or breastfeeding
  • Prior allergic reaction or hypersensitivity to any of the study drug components
  • Active autoimmune disease or history of autoimmune disease that required systemic treatment within 2 years before starting treatment, i.e., with use of disease-modifying agents or immunosuppressive drugs (excluding hypothyroidism, vitiligo, and psoriasis that is controlled with topical management)
  • History or current evidence of any condition, co-morbidity, therapy, that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator
  • Uncontrolled infection with human Immunodeficiency virus (HIV). Patients on stable highly active antiretroviral therapy (HAART) are eligible. Serological testing for HIV at screening is not required
  • Uncontrolled infection with hepatitis B virus. Patients who are receiving or who have received anti-HBV therapy are eligible. Serological testing for HBV at screening is not required
  • Known active hepatitis C virus (HCV) as determined by positive serology and confirmed by polymerase chain reaction (PCR). Patients on or who have received antiretroviral therapy are eligible. Serological testing for HCV at screening is not required
  • Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
  • Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Study Design

Enrollment

100 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Treatment (botensilimab and balstilimab)

Patients receive botensilimab IV, over 30 minutes, on day 1 and balstilimab IV, over 30 minutes, on days 1, 15, 29 and 43 in the absence of disease progression or unacceptable toxicity. 5-16 weeks later, patients then undergo standard of care resection surgery. Patients undergo CT scan and/or MRI and blood sample collection throughout the study.

Interventions

Balstilimab

Given IV

Biospecimen Collection

Undergo blood sample collection

Botensilimab

Given IV

Computed Tomography

Undergo CT scan

Magnetic Resonance Imaging

Undergo MRI

Primary outcome measure

  • Two-year disease-free survival rate [ Time Frame: At 2 years post enrollment ]

Central Contacts and Locations

Central contacts

Sebastian Perez

6262184357sebperez@coh.org

Locations

CTCA at Western Regional Medical Center

Recruiting

Goodyear, Arizona, United States, 85338

Contacts

Pashtoon M. Kasi

949-671-4673kasi@coh.org

Principal Investigator:

Pashtoon M. Kasi

City of Hope Corona

Recruiting

Corona, California, United States, 92882

Contacts

Pashtoon M. Kasi

949-671-4673kasi@coh.org

Principal Investigator:

Pashtoon M. Kasi

City of Hope Medical Center

Recruiting

Duarte, California, United States, 91010

Contacts

Pashtoon M. Kasi

949-671-4673kasi@coh.org

Principal Investigator:

Pashtoon M. Kasi

City of Hope Seacliff

Recruiting

Huntington Beach, California, United States, 92648

Contacts

Pashtoon M. Kasi

949-671-4673kasi@coh.org

Principal Investigator:

Pashtoon M. Kasi

City of Hope at Irvine Lennar

Recruiting

Irvine, California, United States, 92618

Contacts

Pashtoon M. Kasi

949-671-4673kasi@coh.org

Principal Investigator:

Pashtoon M. Kasi

City of Hope at Long Beach Elm

Recruiting

Long Beach, California, United States, 90813

Contacts

Pashtoon M. Kasi

949-671-4673kasi@coh.org

Principal Investigator:

Pashtoon M. Kasi

City of Hope South Pasadena

Recruiting

South Pasadena, California, United States, 91030

Contacts

Pashtoon M. Kasi

949-671-4673kasi@coh.org

Principal Investigator:

Pashtoon M. Kasi

City of Hope Upland

Recruiting

Upland, California, United States, 91786

Contacts

Pashtoon M. Kasi

949-671-4673kasi@coh.org

Principal Investigator:

Pashtoon M. Kasi

City of Hope Atlanta Cancer Center

Recruiting

Newnan, Georgia, United States, 30265

Contacts

Pashtoon M. Kasi

949-671-4673kasi@coh.org

Principal Investigator:

Pashtoon M. Kasi

City of Hope at Illinois Chicago Downtown

Recruiting

Chicago, Illinois, United States, 60611

Contacts

Pashtoon M. Kasi

949-671-4673kasi@coh.org

Principal Investigator:

Pashtoon M. Kasi

City of Hope at Chicago

Recruiting

Zion, Illinois, United States, 60099

Contacts

Pashtoon M. Kasi

949-671-4673kasi@coh.org

Principal Investigator:

Pashtoon M. Kasi

More Information

Sponsor

City of Hope Medical Center

Last update posted

Jul 1, 2026

Last verified

Jun, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by City of Hope Medical Center on 2026-07-01.